Provided herein are processes for the preparation of 2-amino-5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine from 4-chloro-2,5-dimethoxypyrimidine.
U.S. Pat. No. 6,005,108 describes certain substituted 2-amino-5,8-dialkoxy[1,2,4]-triazolo[1,5-c]pyrimidine compounds and their use as intermediates for the preparation of sulfonamide herbicides. 2-Amino-5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine is a useful intermediate for the preparation of penoxsulam. Monatsh. Chem. 1983, 114, 789 describes the preparation of certain (amino)carbonothioylcarbamates followed by their reaction with hydroxylamine and subsequent cyclization to [1,2,4]triazolo[1,5-a]pyrimidin-2-amines. WO 2009/047514 A1 describes the preparation of certain (amino)carbonothioylcarbamates followed by their reaction with hydroxylamine and subsequent cyclization to [1,2,4]triazolo[1,5-a]pyridine and [1,2,4]triazolo[1,5-c]pyrimidine compounds. U.S. Pat. No. 6,559,101 B2 describes the preparation of certain (amino)carbonothioylcarbamates followed by their reaction with hydroxylamine and subsequent cyclization to pyrimidine-substituted [1,2,4]triazolo[1,5-a]pyrimidin-2-amines.
U.S. Pat. No. 6,362,335 B2 describes the production of 2-amino-5,8-dimethoxy[1,2,4]-triazolo[1,5-c]pyrimidine from 2,4-dichloro-5-methoxypyrimidine or 4-chloro-2,5-dimethoxypyrimidine in a multistep process that involves both hydrazine and a cyanogen halide. Hydrazine presents a severe explosion hazard and is toxic by ingestion, inhalation and skin adsorption. It is classified as a carcinogen and has a threshold limit value (TLV) of 0.1 ppm in air. Cyanogen halides are highly irritating and very poisonous. It would be advantageous to produce 2-amino-5,8-dialkoxy[1,2,4]triazolo[1,5-c]pyrimidines efficiently and in high yield by a manufacturing process that avoids hydrazine and cyanogen halide.